According to recent estimates, 36.1 million persons worldwide are infected with human immunodeficiency virus (“HIV”) (Gottlieb M S, 2001 N Engl J Med 344(23):1788–91 and Sepkowitz K A. 2001 N Engl J Med 344(23):1764–72). There are currently a number of anti-retroviral drugs available for clinical use, and these have lead to significant reductions in morbidity and mortality for HIV-infected individuals. Contemporary treatment of HIV infected patients in the United States is generally combination antiretroviral therapy with at least two of three classes of antiretroviral therapy: nucleoside analog reverse transcriptase (RT) inhibitors (NRTI), non-nucleoside analog RT inhibitors (NNRTI), and protease inhibitors. The individual agents in the combination therapy can select for drug-resistant strains and thereby create a reservoir of multidrug resistant HIV that can limit future treatment options.
Currently available anti-HIV agents have been developed against subtype B HIV-1 strains, the predominant HIV strains in the USA and Europe. However, the majority of HIV-infected individuals worldwide are infected with non-subtype B strains, and the majority of new infections worldwide, including the USA and Europe, are caused by non-subtype B strains (Hu et al. 1996 JAMA 275: 210–6; Richman D D et al., In: Current Protocols in Immunology, John Wiley & Sons, Inc., Brooklyn, N.Y., Suppl 8, Unit 12.9, pp. 1–21, 1993). These non-subtype B strains are generally unaffected by commonly used anti-HIV treatment protocols.
Therefore, there is a need to identify potent and effective anti-HIV agents that have activity against resistant strains, including known drug resistant strains and non-subtype B strains of HIV.